Blacks bear a disproportionate burden of asthma morbidity and mortality. In its 2005 report on ethnic disparities in health care, AHRQ identified hospital admissions for asthma as the second largest disparity in quality of health care for Blacks versus Whites. Long-acting beta-agonists (LABAs), a popular treatment option for asthma, are in a class of drugs acting at ADRB2, which have been associated with rare loss of long-term asthma control and increased serious adverse outcomes including death and respiratory failure, even when used with ICS. The risk appears to be four to five-folds greater in Blacks than non-Black patients with asthma. Comparison of studies with LABA/ICS in Blacks versus studies where Blacks were a small minority suggests that Blacks may have much less benefit than other racial groups. Additionally, recent data (Wechsler 2009) suggest that a polymorphism at the 16th position of the ADRB2 gene identifies a group of Blacks (those homozygous for arginine (Arg16Arg)) in whom the response of adding a LABA to an ICS is further diminished. This polymorphism is present in ~20% of U.S. Blacks. In order to address the resulting knowledge gaps, a study is proposed to determine, in a one year practice-based, real-world, randomized, prospective, parallel group, longitudinal comparative effectiveness trial with the clinically important primary outcome of asthma exacerbations, whether in self-identified Black patients with asthma, treatment with LABA/ICS is superior to use of a non-2-adrenergic bronchodilator (tiotropium) combined with ICS (Tio/ICS). The study will also aim to determine, whether in the 20% of self-identified Black patients with asthma bearing Arg16Arg of ADRB2, treatment with LABA/ICS is superior to use of a non-2-adrenergic bronchodilator combined with ICS. PUBLIC HEALTH RELEVANCE: The results of this study will provide the information necessary to make evidence-based, individualized, recommendations concerning treatment algorithms and potential alternative treatment recommendations for the 3.5 million Blacks with asthma. The performance of this study in real life primary care settings will hasten the translation of these findings into day to day practice for this minority population that experiences a disproportionate burden of asthma and has been underrepresented in previous asthma studies.